This is an application for renewal of a Program Project directed at the physiological basis of pulmonary disease. The research will be focused on the mechanisms of bloodflow and ventilation in the lung, and the relationships between these and pulmonary gas exchange. The Program Project is broadly based, interdisciplinary and interdepartmental. The interdepartmental basis is emphasized by the fact that while the first three Research Units are based in the Department of Medicine, the other three are from the Departments of Applied Mechanics and Engineering Sciences (Bioengineering), Mathematics, and the Marine Biology Research Division of the Scripps Institution of Oceanography. The factors controlling ventilation and bloodflow in the lung will be studied by Research Units 1, 2 and 4. A variety of techniques will be used including electron microscopy of rapidly frozen lung, measurements made during short periods of weightlessness in a high performance aircraft, and a biomechanical analysis of lung elasticity. Research on pulmonary gas exchange will be pursued by Research Units 2, 3, 5 and 6. Methods include the multiple inert gas infusion technique for determining distributions of ventilation-perfusion ratios both under steady state and transient conditions, experimental and theoretical analyses of the kinetics of CO2, O2 and CO exchange with blood, theoretical analyses of properties of distributions of ventilation-perfusion ratios, and gas exchange during rest and exercise of 3 species of diving mammals. The six research units will be supported by three shared core facilities devoted to morphometry, computing, and administration. This unusually broadly based program has been effective over the past three years in promoting increased collaboration between departments outside the School of Medicine and those within it, and we expect that its renewal will further the ultimate goal of a better understanding of the physiological basis of pulmonary disease.